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February 18, 2005

Researchers Make Gains on Stem Cell Lines

by Sam Savage

SAN FRANCISCO (AP) -- San Diego researchers recently confirmed scientifically what biologists knew intuitively: The stem cell lines President Bush approved for federally funded research are contaminated by the mouse "feeder cells" used to make them grow in the lab.

The race is now on to create and keep human embryonic stem cells alive without help from mice. Scientists and federal regulators fear the mice cells will transmit animal viruses and lead to immune systems rejecting the drugs created to treat people, making the lines useless for patients.

On Thursday, researchers with the WiCell Research Institute lab at the University of Wisconsin published a paper detailing the latest breakthrough in eliminating mouse cells from the human embryonic stem cell equation.

"This is a major step," said Ren-He Xu, the lead author of the paper, which was published in Nature Methods, a scientific journal. "This work completely gets rid of the need for feeder cells."

Co-author Jamie Thomson was the first to discover human embryonic stem cells in 1998.

Human embryonic stem cells are created in the first days after conception and are the building blocks of the human body. Scientists believe they someday will be able to coax stem cells to turn into healthy cells to treat a wide range of ailments, including diabetes, heart disease and spinal cord injuries.

Many social conservatives who believe life begins at conception view the work as immoral because days-old embryos are destroyed during research.

No one has yet to be treated by stem cells because of many basic technical hurdles, including how to overcome immune-rejection issues and ensure patients aren't otherwise harmed by the treatments.

Scientists have been attempting to solve these and other problems by growing stem cells in the lab and experimenting with them in petri dishes or injecting them into animals. The most popular technique for keeping the stem cells propagating in the lab is to layer them over "feeder cells" derived from mice, a 25-year-old process developed when the embryonic stem cells were first isolated in rodents.

But scientists have been looking for a way to grow the cells without using animals, fearing the mouse cells will harm patients by passing along rodent viruses or provoking an immune response.

Johns Hopkins University researchers have grown stem cells in a stew of cells taken from human bone marrow. In Singapore, scientists connected to the biotech company ES Cell were the first to eliminate the need for mice by using feeder cells derived from fetuses and the reproductive tract of women.

But those and other techniques using human feeder cells come with ethical and scientific baggage. The Singapore work, for instance, was criticized by abortion foes for using fetuses. Additionally, human feeder cells have the potential to pass on human diseases such as AIDS and hepatitis.

"The holy grail is to get away from the feeder cells completely," said Dr. Robert Lanza, a researcher at stem cell company Advanced Cell Technology in Worcester, Mass.

Lanza said Advanced Cell is pursuing its own strategy to grow human embryonic stem cells without the need for feeder cells.

Menlo Park-based Geron Corp. (GERN) holds at least two patents related to its technique of growing human embryonic stem cells with a human protein and a growth factor, eliminating the need altogether for feeder cells.

The work of the Wisconsin researchers is the latest breakthrough in that quest, even though it hasn't completely eliminated all the animal particles from the process.

Xu said his work improves upon other mouse-free advances in which scientists have succeeded in removing mouse cells from their research by growing the stem cells in a soup of human feeder cells.

Xu and his colleagues have boiled the process down to a single, genetically engineered molecule, eliminating the need for human feeder cells.

They say they've streamlined a complicated and tedious process for nurturing stem cells that has prevented many scientists from attempting their own experiments.

"It is important that the culture of human (stem) cells be simplified so that the average scientist can use them without extensive prior training," Thomson said. "This development is a good step in that direction."

Still, Thomson and others remain concerned about animal contamination even with this latest breakthrough. That's because the new technique still requires the use of priming agents that contain animal particles.

That's something Xu said he and his colleagues continue to work on. He said they are optimistic that they will soon eliminate all animal molecules from the stem cell equation.

"I think it is indeed a major step forward to eliminate the need for a mouse feeder layer in culturing human embryonic stem cells," Dr. Ajit Varki of the University of California, San Diego said in an e-mail interview. "However, with regard to the problem of 'contamination,' they have not solved the problem."

Varki co-wrote the paper last month that confirmed the contamination of the Bush-approved stem cell lines.